Iodine → (R)-2-chloro-4-(1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-3-methylbenzonitrile

HRID 238571Notes

Reaction equation

HRID 238571 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.II.CCN(CC)CC.[Cl:29][C:30]1[C:31]([CH3:58])=[C:32]([NH:38][C@H:39]([C:54]([OH:57])([CH3:56])[CH3:55])[C:40]([NH:42][NH:43][C:44](=[O:53])[C:45]2[CH:50]=[CH:49][C:48]([C:51]#[N:52])=[CH:47][CH:46]=2)=O)[CH:33]=[CH:34][C:35]=1[C:36]#[N:37]>C(Cl)Cl.C1COCC1>[Cl:29][C:30]1[C:31]([CH3:58])=[C:32]([NH:38][C@@H:39]([C:40]2[O:53][C:44]([C:45]3[CH:46]=[CH:47][C:48]([C:51]#[N:52])=[CH:49][CH:50]=3)=[N:43][N:42]=2)[C:54]([OH:57])([CH3:55])[CH3:56])[CH:33]=[CH:34][C:35]=1[C:36]#[N:37]

Participants

7

Reactant 4

HCID 807Iodine2×HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 66625521(R)-N'-(2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-3-methylbutanoyl)-4-cyanobenzohydrazide

Product 1

HCID 56598016(R)-2-chloro-4-(1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-3-methylbenzonitrileYield 90%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of triphenylphosphine (1.70 g, 6.48 mmol) in DCM (50 mL) was added I2 (1.63 g, 6.42 mmol) at 0° C. After all the Iodine was dissolved completely, Et3N (1.8 mL, 12.9 mmol) was added, followed by a solution of (R)—N′-(2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-3-methylbutanoyl)-4-cyanobenzohydrazide (1.37 g, 3.22 mmol) in DCM (10 mL) and THF (10 mL). After addition, the reaction mixture was allowed to warm to room temperature and stirred for additional 30 min. The reaction was quenched with saturated aq. sodium thiosulfate (10 mL) and diluted with DCM (100 mL). The organic layer was separated and washed with water, brine and dried over Na2SO4. After the solvent was removed, the residue was purified by flash chromatography to provide the title compound (R)-2-chloro-4-(1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxy-2-methylpropylamino)-3-methylbenzonitrile (1.18 g, 90%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.19 (d, J=8.8 Hz, 2H), 7.97 (d, J=8.8 Hz, 2H), 7.46 (d, J=8.6 Hz, 1H), 6.80 (d, J=8.6 Hz, 1H), 5.71 (d, J=9.0 Hz, 1H), 5.14 (d, J=9.0 Hz, 1H), 4.67 (s, 1H), 2.39 (s, 3H), 1.53 (s, 3H), 1.36 (s, 3H).

Workup

  1. additionAfter addition
  2. customThe reaction was quenched with saturated aq. sodium thiosulfate (10 mL)
  3. additiondiluted with DCM (100 mL)
  4. customThe organic layer was separated
  5. washwashed with water, brine
  6. dry with materialdried over Na2SO4
  7. customAfter the solvent was removed
  8. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-e591e9d8f45340ec9e2ff595fb255b5a
Source dataset
uspto-grants-2014_02
Patent number
US08642632B2

Reaction notes

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